Vericiguat Drug-drug Interaction Study With Isosorbite Mononitrate in Stable Coronary Artery Disease Patients

Multi-center, Randomized, Placebo-controlled, Double-blind Group Comparison Study to Investigate Safety, Tolerability and Blood Pressure of 2.5 mg, 5.0 mg and 10 mg Vericiguat Each Given Over 14 ± 3 Days Together With Isosorbite Mononitrate (ISMN) 60 mg Extended Release Formulation After a Pretreatment Phase (ISMN-starting Dose: 30 mg) in Stable Coronary Artery Disease (CAD) Patients With or Without Heart Failure Aged 30 to 80 Years - Vericiguat ISOsoRbite Mononitrate Interaction (VISOR) Study

This study is intended to investigate the pharmacodynamic drug-drug interaction as well as the safety and tolerability of isosorbite mononitrate and vericiguat in patients with stable coronary artery disease.

Inclusion Criteria:

Patients with stable CAD defined by

• coronary artery stenosis in any of the 3 main coronary vessels > 50% documented by coronary angiography within last 36 months
• or history of myocardial infarction
• Age: 30 to 80 years (inclusive) at the first screening examination
• Body mass index (BMI): above/equal 18.0 and below/equal 36.0 kg / m²

Exclusion Criteria:

• Intervention e.g. revascularization by percutaneous coronary intervention (PCI) and/or coronary artery bypass graft (CABG) during the last 3 months
• Progressive angina with symptoms of worsening of angina within the < 3 months prior to the first screening examination
• History of recent (< 6 months prior to the first screening examination) myocardial infarction or unstable angina
• Symptomatic carotid stenosis, or transient ischemic attack or stroke within 3 months prior to the first screening examination or patients with stroke at more than 3 months prior to the first screening examination with significant residual neurologic involvement
• Insulin dependent diabetes mellitus
• Clinically relevant cardiac ischemia at screening
• Clinical significant persistent ischemia, which should be ruled out by clinical judgment of the investigator, based on medical history, available clinical data e.g. past angiograms or preexisting or current exercise testing with any imaging technique (e.g. dobutamine stress echocardiography, adenosine or dobutamine stress cardiac magnetic resonance imaging (CMR), scinthigraphy or exercise ECG)
• Atrial fibrillation, pacemaker, defibrillator, atrial ventricular (AV)-block II and III
• Systolic blood pressure below 110 or above 160 mmHg at first screening visit
• Diastolic blood pressure above 100 mmHg at first screening visit
• Heart rate below 50 or above 100 beats / min (taken from ECG measurement) at first screening visit
• Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m*2 at first screening visit